Propionamide → HCID 86703360, compound

HRID 1050845Notes

Reaction equation

HRID 1050845 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([N+:16]([O-:18])=[O:17])=[CH:11][C:10]=2[F:19])[CH:5]=[CH:4][N:3]=1.[C:20]([NH2:24])(=[O:23])[CH2:21][CH3:22].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:19][C:10]1[CH:11]=[C:12]([N+:16]([O-:18])=[O:17])[C:13]([F:15])=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:24][C:20](=[O:23])[CH2:21][CH3:22])[CH:7]=1

Participants

7

Reactant 3

HCID 6578PropionamideHCID 10796Cesium carbonateHCID 552369312-Chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine

Product 1

HCID 86703360HCID 86703360, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of Example A1 (35 g, 122 mmol) in anhydrous 1,4-dioxane (900 mL) was degassed with nitrogen for 10 min and to it was added propionamide (10.5 g, 143 mmol), 1,1′-bis(diphenylphosphino) ferrocene (dppf, 6.6 g, 12.0 mmol, 0.1 equiv.), Cs2CO3 (58.4 g, 179 mmol) and Pd2(dba)3 (5.47 g, 5.97 mmol). The mixture was degassed with nitrogen for another 15 min and then heated to 85° C. (internal temp) and stirred at that temp for 4 h. The reaction mixture was cooled to RT, filtered through a bed of diatomaceous earth and washed with EtOAc (1 L). The combined filtrates were concentrated under reduced pressure and purified by a silica gel chromatography (EtOAc/hexanes) to afford 30 g. This material was further purified by a trituration with diisopropyl ether (600 mL) and drying under vacuum at 40° C. to provide N-(4-(2,5-difluoro-4-nitrophenoxy)pyridin-2-yl)propionamide (27.2 g, 69% yield). MS (ESI): m/z 324.1 (M+H+). This material was carried to next step without further purification.

Workup

  1. customThe mixture was degassed with nitrogen for another 15 min
  2. temperatureThe reaction mixture was cooled to RT
  3. filtrationfiltered through a bed of diatomaceous earth
  4. washwashed with EtOAc (1 L)
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. custompurified by a silica gel chromatography (EtOAc/hexanes)
  7. customto afford 30 g
  8. customThis material was further purified by a trituration with diisopropyl ether (600 mL)
  9. customdrying under vacuum at 40° C.

Sources & evidence

ORD record
ord-617e698dbd354329af5aafd7ea5c7f5e
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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